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Yorodumi- PDB-6vhl: Paired Helical Filament from Alzheimer's Disease Human Brain Tissue -
+Open data
-Basic information
Entry | Database: PDB / ID: 6vhl | |||||||||
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Title | Paired Helical Filament from Alzheimer's Disease Human Brain Tissue | |||||||||
Components | Microtubule-associated protein tauTau protein | |||||||||
Keywords | PROTEIN FIBRIL / Pathological amyloid fibril cross-beta fold parallel beta-sheets | |||||||||
Function / homology | Function and homology information plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / regulation of chromosome organization / positive regulation of protein localization / rRNA metabolic process / internal protein amino acid acetylation / regulation of mitochondrial fission / intracellular distribution of mitochondria / axonal transport of mitochondrion / axon development / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / protein polymerization / negative regulation of mitochondrial fission / axolemma / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / supramolecular fiber organization / Activation of AMPK downstream of NMDARs / regulation of microtubule cytoskeleton organization / cytoplasmic microtubule organization / stress granule assembly / regulation of cellular response to heat / axon cytoplasm / regulation of calcium-mediated signaling / positive regulation of microtubule polymerization / cellular response to brain-derived neurotrophic factor stimulus / somatodendritic compartment / synapse assembly / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / synapse organization / response to lead ion / microglial cell activation / regulation of synaptic plasticity / Hsp90 protein binding / PKR-mediated signaling / protein homooligomerization / cytoplasmic ribonucleoprotein granule / memory / microtubule cytoskeleton organization / cellular response to reactive oxygen species / SH3 domain binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / protein-macromolecule adaptor activity / single-stranded DNA binding / cell-cell signaling / cellular response to heat / cell body / actin binding / growth cone / protein-folding chaperone binding / double-stranded DNA binding / microtubule binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / neuron projection / nuclear speck / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Arakhamia, T. / Lee, C.E. / Carlomagno, Y. / Duong, D.M. / Kundinger, S.R. / Wang, K. / Williams, D. / DeTure, M. / Dickson, D.W. / Cook, C.N. ...Arakhamia, T. / Lee, C.E. / Carlomagno, Y. / Duong, D.M. / Kundinger, S.R. / Wang, K. / Williams, D. / DeTure, M. / Dickson, D.W. / Cook, C.N. / Seyfried, N.T. / Petrucelli, L. / Fitzpatrick, A.W.P. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell / Year: 2020 Title: Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains. Authors: Tamta Arakhamia / Christina E Lee / Yari Carlomagno / Duc M Duong / Sean R Kundinger / Kevin Wang / Dewight Williams / Michael DeTure / Dennis W Dickson / Casey N Cook / Nicholas T Seyfried ...Authors: Tamta Arakhamia / Christina E Lee / Yari Carlomagno / Duc M Duong / Sean R Kundinger / Kevin Wang / Dewight Williams / Michael DeTure / Dennis W Dickson / Casey N Cook / Nicholas T Seyfried / Leonard Petrucelli / Anthony W P Fitzpatrick / Abstract: Tau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures ...Tau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures associated with individual tauopathies. Here, we use cryo-electron microscopy (cryo-EM) to determine the structures of tau filaments from corticobasal degeneration (CBD) human brain tissue. Cryo-EM and mass spectrometry of tau filaments from CBD reveal that this conformer is heavily decorated with posttranslational modifications (PTMs), enabling us to map PTMs directly onto the structures. By comparing the structures and PTMs of tau filaments from CBD and Alzheimer's disease, it is found that ubiquitination of tau can mediate inter-protofilament interfaces. We propose a structure-based model in which cross-talk between PTMs influences tau filament structure, contributing to the structural diversity of tauopathy strains. Our approach establishes a framework for further elucidating the relationship between the structures of polymorphic fibrils, including their PTMs, and neurodegenerative disease. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6vhl.cif.gz | 36.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6vhl.ent.gz | 24.7 KB | Display | PDB format |
PDBx/mmJSON format | 6vhl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vh/6vhl ftp://data.pdbj.org/pub/pdb/validation_reports/vh/6vhl | HTTPS FTP |
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-Related structure data
Related structure data | 21207MC 6vh7C 6vhaC 6vi3C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 8370.578 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPT, MAPTL, MTBT1, TAU / Production host: Homo sapiens (human) / References: UniProt: P10636 #2: Chemical | ChemComp-GLY / |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: Paired Helical Filament from Alzheimer's Disease Human Brain TissueTauopathy Type: TISSUE / Entity ID: #1 / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Helical symmerty | Angular rotation/subunit: 179.417 ° / Axial rise/subunit: 2.353 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 156840 / Symmetry type: HELICAL |